The first objective of this research is to determine whether reversible binding of a drug to body proteins via drug-metal ion-protein ternary complexes can result in antigenic determinants sufficiently stable to produce allergic sensitization. Since the penicillin allergic response is a major medical problem, this will be our primary area of interest. Our previous studies have shown that reasonably strong penicilloic acid-metal ion-amino acid ternary complexes can form under physiologic conditions. Therefore, the chemistry of the formation and degradation of the penicilloic acids will be studies through use of kinetic techniques involving pH stat and molar rotation studied. The strength and type of binding between either penicilloic acid and/or its degradation products with various amino acids, polypeptides, and proteins mediated through various metal ions will be studied utilizing spectrophotometric, potentiometric or equilibrium dialysis methods. Each of the complexes will be tested for immunogenicity utilizing precipitin reactions, hemagglutination reactions, or skin tests. The sulfa drugs and salicylates will be included among other immunogenic but non reactive drug to be studied. A second objective will be to investigate the mechanism whereby certain chelating agents eliminate or reduce the resistance of microorganisms to antibiotic such as penicillin G, ampicillin, chloramphenicol and tetracycline.